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Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes Gautier JF; Fetita S; Sobngwi E; Salaun-Martin CDiabetes Metab 2005[Jun]; 31 (3 Pt 1): 233-42Incretin hormones are defined as intestinal hormones released in response to nutrient ingestion, which potentiate the glucose-induced insulin response. In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide GIP, and glucagon-like peptide-1 GLP-1. GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. Their effect is mediated through their binding with specific receptors, though part of their biological action may also involve neural modulation. GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. As the insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide was a candidate as a therapeutic agent for this disease. A number of pharmacological strategies have been developed to provide continuous delivery of GLP-1 and to prevent degradation of GLP-1, including continuous administration of GLP-1, DPP-IV inhibitors and DPP-IV resistant GLP-1 analogues. Recent results of the most clinically advanced incretin mimetics confirmed their efficacy to improve glycemic control in type 2 diabetic patients. Further results are expected to confirm the efficacy/safety profile of these compounds, and to find their place in the therapeutic strategy of type 2 diabetes.|Diabetes Mellitus, Type 2/*drug therapy[MESH]|Dipeptidyl Peptidase 4/metabolism[MESH]|Gastric Inhibitory Polypeptide/administration & dosage/physiology/*therapeutic use[MESH]|Glucagon-Like Peptide 1[MESH]|Glucagon/administration & dosage/*therapeutic use[MESH]|Humans[MESH]|Infusions, Intra-Arterial[MESH]|Insulin Secretion[MESH]|Insulin/metabolism[MESH]|Intestine, Small/physiopathology[MESH]|Peptide Fragments/administration & dosage/*therapeutic use[MESH]|Protein Precursors/administration & dosage/*therapeutic use[MESH] |
